Review
Genetics & Heredity
Carina A. Dehner, Amy E. Armstrong, Marielle Yohe, Jack F. Shern, Angela C. Hirbe
Summary: Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents, but the prognosis has not significantly improved in recent years. Researchers are working to better understand the genetic abnormalities and risk stratification of the disease in order to develop more effective therapeutic strategies.
Article
Multidisciplinary Sciences
Xiong Shu, Weifeng Liu, Huiqi Liu, Hui Qi, Chengai Wu, Yu-Liang Ran
Summary: This study identified differential expression of miRNAs between CD133(+) and CD133(-) cells, with miR-4284 being a particularly interesting miRNA that may have significant roles in the function of OSCs, especially associated with the Wnt signaling pathway.
Article
Biochemistry & Molecular Biology
Yan S. Kim, Daria M. Potashnikova, Alisa M. Gisina, Irina Kholodenko, Arthur T. Kopylov, Olga Tikhonova, Leonid K. Kurbatov, Aleena A. Saidova, Anna Tvorogova, Roman Kholodenko, Pavel Belousov, Ivan A. Vorobjev, Victor G. Zgoda, Konstantin N. Yarygin, Alexey Yu Lupatov
Summary: CD133 plasma membrane expression is positively correlated with the proliferative activity of cancer cells. Transcriptomic and proteomic profiling revealed minor distinctions between different levels of CD133 expression. The TRIM28 transcription factor plays a prominent role in regulating CD133 expression. Knockout of the TRIM28 gene downregulates CD133 expression in Caco2 cell clones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Na-Mei Li, Shi-He Jiang, Peng Zhou, Xiao-Hong Li
Summary: This study reports a rare case of an 11-year-old patient with ERMS who tested positive for MEF2D-NTRK1 fusion. The case report provides a comprehensive overview of the clinical, radiographic, histopathological, immunohistochemical, and genetic characteristics of a palpebral ERMS. Additionally, it sheds light on the uncommon occurrence of NTRK1 fusion-positive ERMS, which may have implications for therapy and prognosis.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dong-Wook Min, Hwang-Phill Kim, Jinhyun Kim, Xianyu Wen, Sungsik Kim, Young-Won Cho, Yoojoo Lim, Sang-Hyun Song, Sae-Won Han, Sunghoon Kwon, Gyeong Hoon Kang, Tae-You Kim
Summary: Tumor heterogeneity in colon cancer therapy poses challenges, with single cell analysis revealing heterogeneous subclones within CD133 positive cancer stem cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, General & Internal
Lucia Lisa Petrilli, Federica Riccio, Giulio Giuliani, Alessandro Palma, Cesare Gargioli, Simone Vumbaca, Monika Faron, Graziana Palmieri, Luca Pasquini, Francesca Sacco, Gianni Cesareni, Luisa Castagnoli, Claudia Fuoco
Summary: The study utilized mass cytometry to reveal the crucial role of fibro/adipogenic progenitors (FAPs) in the development of embryonal rhabdomyosarcoma (eRMS). In vitro studies showed that only infected FAPs had an antigen profile similar to eRMS cells, supporting their involvement in eRMS development.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Mustafa Karabicici, Sena Alptekin, Zeynep Firtina Karagonlar, Esra Erdal
Summary: Therapeutic induction of senescence may increase cancer stem cell phenotype, leading to increased tumor aggressiveness and disease recurrence. In liver cancer cells, doxorubicin can induce cellular senescence, increase stem cell gene expression, and cause a shift in stem cell characteristics.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Jimin Park, Seung Ki Kim, Steffanus Pranoto Hallis, Bo-Hyun Choi, Mi-Kyoung Kwak
Summary: This study investigated the potential relationship between the CSC marker CD133 and the master transcription factor NRF2 in colon cancer. The results indicate that the CD133/NRF2 axis plays a critical role in the development of CSC-like properties in colon cancer cells, with activation of the PI3K/AKT signaling pathway involved in CD133-mediated NRF2 activation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, General & Internal
Joanna Radzikowska, Anna M. Czarnecka, Teresa Klepacka, Magdalena Rychlowska-Pruszynska, Anna Raciborska, Bozenna Dembowska-Baginska, Maciej Pronicki, Andrzej Kukwa, Wojciech Fendler, Urszula Smyczynska, Wojciech Kukwa, Antoni Krzeski
Summary: This study aimed to assess the expression and prognostic role of cancer stem cell (CSC) markers in pediatric rhabdomyosarcoma (RMS). The expression of selected CSC markers was confirmed in RMS tissue, but no significant correlation was found with clinical and pathological prognostic factors. Further studies are needed to fully understand the relevance of these CSC markers in RMS carcinogenesis.
Article
Oncology
Chuquan Shang, Bardes Hassan, Moinul Haque, Yuqi Song, Jing Li, Dongzhe Liu, Eva Lipke, Will Chen, Sylvie Giuriato, Raymond Lai
Summary: The study demonstrated that inhibiting autophagy in ALK + ALCL can increase drug sensitivity in stem-like cells, with differential Myc gene expression playing a critical role in this process. Stem-like cells have a greater impact on the efficacy of therapeutic drugs, indicating their crucial role in drug resistance.
Article
Oncology
Alisa Gisina, Svetlana Novikova, Yan Kim, Dmitry Sidorov, Stanislav Bykasov, Nadezhda Volchenko, Andrey Kaprin, Victor Zgoda, Konstantin Yarygin, Alexey Lupatov
Summary: By comparative proteomic profiling, biomarkers of CD133-positive colorectal cancer stem cells were revealed, with high expression of CEACAM5 confirmed in these cells. Knockout of CD133 did not significantly affect CEACAM5 expression levels, but resulted in increased variance in the percentage of CEACAM5-positive cells.
Article
Oncology
Madeline Fritzke, Kenian Chen, Weiliang Tang, Spencer Stinson, Thao Pham, Yadong Wang, Lin Xu, Eleanor. Y. Y. Chen
Summary: Rhabdomyosarcoma (RMS) is a devastating pediatric soft tissue sarcoma with no effective therapy for relapsed disease. The study revealed that vincristine treatment increased CD133-positive stem-like resistant cells in RMS cells. Targeting MYC and YBX1 using CRISPR/Cas9 reduced stem-like characteristics and viability of vincristine-resistant cells. The MYC-YBX1 axis holds promise for improving survival in RMS patients.
Article
Neurosciences
Shelanah Salih, Zubair Ahmed Nizamudeen, Nigel De Melo, Lisa Chakrabarti, Virginie Sottile
Summary: Recent observations suggest that Bergmann glia in the cerebellum may play a role in tissue repair due to their expression of neural stem cell markers, although the physiological relevance of this overlap remains unclear in the absence of established in vivo evidence of tissue regeneration in the adult cerebellum.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alvaro Centron-Broco, Francesca Rossi, Chiara Grelloni, Raffaele Garraffo, Dario Dattilo, Andrea Giuliani, Gaia Di Timoteo, Alessio Colantoni, Irene Bozzoni, Manuel Beltran Nebot
Summary: In this study, a circular RNA called circAFF1 was found to be overexpressed in alveolar rhabdomyosarcoma. Depletion of circAFF1 was shown to affect cell homeostasis and promote cell migration through the downregulation of genes involved in cell adhesion pathways. These findings highlight the potential of circAFF1 as a future therapeutic target for alveolar rhabdomyosarcoma.
Article
Cell Biology
Mohammed R. Shaker, Amna Kahtan, Renuka Prasad, Ju-Hyun Lee, Giovanni Pietrogrande, Hannah C. Leeson, Woong Sun, Ernst J. Wolvetang, Andrii Slonchak
Summary: The study reveals the important role of NELL2 in human brain development, specifically in neuronal differentiation, polarization, and axon guidance. The expression pattern of NELL2 varies in different cell stages and it is also implicated in human white matter diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Semjon Sidorov, Lara Fux, Katja Steiner, Samyo Bounlom, Sabrina Traxel, Tarik Azzi, Arbeneshe Berisha, Christoph Berger, Michele Bernasconi, Felix K. Niggli, Yvonne Perner, Sugeshnee Pather, Werner Kempf, David Nadal, Simone Burgler
Summary: The study reveals the dichotomous effects of CD4 + T cells in endemic Burkitt lymphoma, suggesting that they may suppress cancer development by killing pre-cancerous cells without specific translocations, but also indirectly promote cancer progression by inducing EBV latency switching. Moreover, it demonstrates how CD4 + T cells can impact cancer pathogenesis and progression, providing a new in vitro model for further research on the role of IgH/c-myc translocations.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Zeljko Antic, Jiangyan Yu, Beat C. Bornhauser, Stefan H. Lelieveld, Cedric G. van der Ham, Simon van Reijmersdal, Lionel Morgado, Sarah Elitzur, Jean-Pierre Bourquin, Giovanni Cazzaniga, Cornelia Eckert, Mireia Camos, Rosemary Sutton, Helene Cave, Anthony Moorman, Edwin Sonneveld, Ad Geurts van Kessel, Frank N. van Leeuwen, Peter M. Hoogerbrugge, Esme Waanders, Roland P. Kuiper
Summary: Early relapses in BCP-ALL often arise from minor subclones at diagnosis. Understanding the therapeutic pressure driving these events may help develop improved therapies.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Hematology
Kristina Mueller, Fotini Vogiatzi, Dorothee Winterberg, Thies Rosner, Lennart Lenk, Lorenz Bastian, Carina L. Gehlert, Marie-Pauline Autenrieb, Monika Bruggemann, Gunnar Cario, Martin Schrappe, Andreas E. Kulozik, Cornelia Eckert, Anke K. Bergmann, Beat Bornhauser, Jean-Pierre Bourquin, Thomas Valerius, Matthias Peipp, Christian Kellner, Denis M. Schewe
Summary: This study suggests that combining CD47 blockade with Dara is a promising therapy for T-ALL, especially for relapsed/refractory disease harboring a dismal prognosis in patients.
Article
Oncology
Paulina Richter-Pechanska, Joachim B. Kunz, Tobias Rausch, Busra Erarslan-Uysal, Beat Bornhauser, Viktoras Frismantas, Yassen Assenov, Martin Zimmermann, Margit Happich, Caroline von Knebel-Doeberitz, Nils von Neuhoff, Rolf Kohler, Martin Stanulla, Martin Schrappe, Gunnar Cario, Gabriele Escherich, Renate Kirschner-Schwabe, Cornelia Eckert, Smadar Avigad, Stefan M. Pfister, Martina U. Muckenthaler, Jean-Pierre Bourquin, Jan O. Korbel, Andreas E. Kulozik
Summary: This study investigates the mechanisms of T-ALL relapse and reveals fundamentally different mechanisms driving type-1 and type-2 relapses. Type-1 relapses are characterized by IL7R upregulation, while type-2 relapses involve constitutional cancer predisposition gene mutations, genetic and epigenetic remodeling, and somatic hypermutator phenotypes. The study also finds that T-ALLs that later develop into type-2 relapses already have complex subclonal architecture even at the time of initial diagnosis.
Article
Oncology
Gloria Pedot, Joana Graca Marques, Philip P. Ambuhl, Marco Wachtel, Stephanie Kasper, Quy A. Ngo, Felix K. Niggli, Beat W. Schaefer
Summary: Transcription factor EWS-FLI1 is an oncogenic protein that lacks enzymatic activity and has been considered undruggable. Through a high-throughput drug screen and a global protein stability approach, a compound called fimepinostat was identified as a potential candidate to destabilize EWS-FLI1 protein and reduce Ewing sarcoma tumor progression. This study demonstrates the effectiveness of combining drug screening and protein stability analysis in identifying drugs that can modulate the stability of EWS-FLI1 and paves the way for the development of new therapeutic strategies.
Correction
Oncology
Gloria Pedot, Joana Graca Marques, Philip P. Ambuehl, Marco Wachtel, Stephanie Kasper, Quy A. Ngo, Felix K. Niggli, Beat W. Schafer
Article
Oncology
Dzhangar Dzhumashev, Andrea Timpanaro, Safa Ali, Andrea J. De Micheli, Kamel Mamchaoui, Ilaria Cascone, Jochen Rossler, Michele Bernasconi
Summary: Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in childhood and adolescence. This study explored the use of tumor-targeting peptides to selectively deliver drugs to RMS cells. Among the tested peptides, F3 showed strong and specific binding to RMS cells, effective internalization, and delivery of a toxin. The target of F3 peptide, nucleolin, was found to be expressed on the surface of RMS cells. The results suggest that F3 peptide could be a potential therapeutic approach for RMS.
Article
Biochemistry & Molecular Biology
Andrea Timpanaro, Caroline Piccand, Anne-Christine Uldry, Peter Karl Bode, Dzhangar Dzhumashev, Rita Sala, Manfred Heller, Jochen Rossler, Michele Bernasconi
Summary: Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in children. More effective and less toxic therapies are needed for high-grade and metastatic RMS. Surface proteins profiling revealed potential targets for immunotherapies of RMS, including known targets FGFR4, NCAM1, and CD276/B7-H3, and also newly discovered targets AGRL2, JAM3, MEGF10, GPC4, and CADM2. L1CAM showed strong expression in alveolar RMS tumors, making it a practical target for antibody-based therapies of this subtype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Hyobin Jeong, Karen Grimes, Kerstin K. Rauwolf, Peter-Martin Bruch, Tobias Rausch, Patrick Hasenfeld, Eva Benito, Tobias Roider, Radhakrishnan Sabarinathan, David Porubsky, Sophie A. Herbst, Busra Erarslan-Uysal, Johann-Christoph Jann, Tobias Marschall, Daniel Nowak, Jean-Pierre Bourquin, Andreas E. Kulozik, Sascha Dietrich, Beat Bornhauser, Ashley D. Sanders, Jan O. Korbel
Summary: This study introduces a computational method called scNOVA, which utilizes Strand-seq to analyze structural variations in single cells and infer gene expression. The research reveals the impact of structural variations on gene regulation and signaling pathways, and successfully applies the method to the study of chronic lymphocytic leukemia and T cell acute lymphoblastic leukemia.
NATURE BIOTECHNOLOGY
(2023)
Article
Engineering, Biomedical
Furkan Gokce, Alicia Kaestli, Christian Lohasz, Martina de Geus, Hans-Michael Kaltenbach, Kasper Renggli, Beat Bornhauser, Andreas Hierlemann, Mario Modena
Summary: Despite improving survival rates in pediatric leukemia patients, the outcome for certain subtypes remains poor. A microphysiological drug-testing platform has been developed to address the limitations of current screening methods, allowing for the co-culture of patient-derived leukemia cells, bone marrow cells, and liver tissues. By testing the activation of the prodrug ifosfamide in this platform, sample-specific sensitivities to ifosfamide in primary leukemia samples can be identified, providing potential for precision chemotherapy selection.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Oncology
Silvia Pomella, Sara G. Danielli, Rita Alaggio, Willemijn B. Breunis, Ebrahem Hamed, Joanna Selfe, Marco Wachtel, Zoe S. Walters, Beat W. Schaefer, Rossella Rota, Janet M. Shipley, Simone Hettmer
Summary: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, characterized by aberrant muscle differentiation. Abnormalities in the regulatory transcription factors (MRFs) involved in skeletal muscle development contribute to tumorigenesis in RMS. Core regulatory circuitries (CRCs) and hierarchically organized subsets of cells play a role in maintaining the disease-driving fusion oncogene and promoting malignancy in RMS. Understanding the genetic and epigenetic framework of abnormal muscle differentiation in RMS provides insights into its mechanisms and potential therapeutic strategies.
Article
Oncology
Ewa Koscielniak, Beate Timmermann, Marc Muenter, Jadwiga Weclawek-Tompol, Ruth Ladenstein, Felix Niggli, Gustaf Ljungman, Ines B. Brecht, Bernd Blank, Erika Hallmen, Monika Scheer, Joerg Fuchs, Guido Seitz, Claudia Blattmann, Monika Sparber-Sauer, Thomas Klingebiel
Summary: This study aimed to analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on the prognosis of patients with localized rhabdomyosarcoma (RMS). The study found that low RT doses were comparable in efficacy to high RT doses in patients with favorable risk profiles. RT improved overall survival (OS) in patients with head/neck-parameningeal (HN-PM) tumors. In addition, the study also found that RT could be omitted in patients with IRS I embryonal RMS (eRMS).
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemical Research Methods
Yun Huang, Aneta Drakul, Jasmeet Sidhu, Kerstin K. Rauwolf, James Kim, Beat Bornhauser, Jean-Pierre Bourquin
Summary: Mesenchymal stromal cells (MSCs) play a crucial role in regulating hematopoiesis and may also support cancer cells in evading therapy. This study engineered MSCs to express a synthetic CD19-sensor receptor, allowing for ex vivo drug response profiling of primary CD19+ leukemia cells.
Article
Hematology
Malwine J. Barz, Lena Behrmann, Danaelle Capron, Gabriele Zuchtriegel, Fabio D. Steffen, Leo Kunz, Yang Zhang, Iria Jimenez Vermeerbergen, Blerim Marovca, Moritz Kirschmann, Antonia Zech, Cesar Nombela-Arrieta, Urs Ziegler, Timm Schroeder, Beat Bornhauser, Jean -Pierre Bourquin
Summary: Persistence of residual disease after induction chemotherapy is a strong predictor of relapse in acute lymphoblastic leukemia (ALL). Bone marrow microenvironment plays a role in treatment resistance. By using three-dimensional fluorescence imaging, specific sites in the bone marrow were identified where B-cell precursor ALL cells and T-ALL cells preferentially reside and interact with different components of the microenvironment. These lineage-dependent differences suggest potential targets for improving treatment.